While it is desirable to minimize human exposure to carcinogenic agents, the methods used to identify such agents should depend on endpoints other than the induction of human disease. The use of such methods, the less costly and time consuming the better, necessarily involves assumptions as to their relevance to the human condition. Research into the various aspects of the mechanism of chemical carcinogenesis can thus be said to have as a practical goal the elimination or validation of assumptions made in extrapolating from simple test systems to man. In our program we are specifically investigating the following aspects: (1) identification of the adults formed when aromatic amine carcinogens attack nucleic acids in target tissues, and determination of the susceptibility of such adducts on DNA to repair; (2) theoretical methods for predicting adduct formation (prediction of rate, solvent competition, and product distribution); (3) identification of the immediate mutagenic consequences of each type of lesion; (4) determination of reasons for lack of tumorigenicity in tissues which are chemically attacked by carcinogens; (5) dissection of the initiation and promotion processes in tumor induction.